An Exploratory Study of the Potential for Rational Immune System Manipulation to Prevent Emergence of Synucleinopathy Manifestations in Persons With REM Sleep Behavior Disorder (RBD)

Recruiting now · Phase 2 · Has a placebo group

Conditions studied: REM Sleep Behavior Disorder

In brief

This is a phase 2 study to assess the ability of adalimumab as compared to placebo to reduce or prevent progression of synuclein-related neurodegeneration in persons with idiopathic REM Sleep Behavior Disorder (RBD). The Primary Endpoint will be change from baseline in expression of the Parkinson Disease Related Pattern (PDRP) will be assessed using change in 18-flurodeoxyglucose (FDG) Positron Emission Tomography (PET) imaging.

Key facts

Study ID

NCT06996652

Run by

Yale University

People needed

108

Starts

2026-07-15

Expected to finish

2029-08-01

Last updated by the study team

2026-08-06

Who can join

Age: 50 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Males, or females who are either
• post-menopausal or otherwise not of child-bearing potential, defined as either 1) having had no menses for 12 or months without an alternative medical cause or explanation or 2) having undergone a surgical procedure (hysterectomy, bilateral tubal ligation) that prevents conception, or
• practicing adequate contraception. Female participants of childbearing potential must practice at least 1 protocol-specified method of birth control, that is effective from 30 days before baseline (or earlier) through at least 150 days after the last dose of the study drug. Female participants of non-childbearing potential do not need to use birth control.
• women of childbearing potential must have a negative urine pregnancy test prior to enrollment, and agree to undergo a pregnancy test at each study visit. Women with a positive pregnancy test at screening or at any subsequent study visit will be withdrawn from the study.
• Diagnosis of idiopathic REM Sleep Behavior Disorder (RBD) based upon:
• History of Dream Enactment Behavior during sleep and
• Evidence of REM sleep without muscle atonia based upon polysomnogram obtained in a qualified sleep laboratory, consistent with ICSD-3 Diagnostic Criteria for RBD
• Hyposmia, defined as score < 15th percentile for age-and gender-specific normal values
• Not diagnosed with motor Parkinson's Disease or Lewy Body Dementia
• Have a MoCA score at screening and baseline ≥23
• Able to speak, read and write fluently in the official language of the site's geographical region
• Participant must be willing and able to attend all study visits as required by the study protocol
• Participant must have a study partner who is in regular contact with the subject and can accompany the subject to clinic visits and report on subject's functional status
• Participant must be able to self-inject study drug regularly or have a study partner who is available, willing and able to do so
• Participant must be able to understand the study requirements and provide written informed consent

You may not qualify if…

• Women who are pregnant, planning to become pregnant, or currently breastfeeding
• Alternative explanation or etiology for the presence of RBD (e.g. narcolepsy)
• Other than RBD, neurologic or medical disorder which may impair cognition including: head trauma, seizure disorder, neurodegenerative disease, hydrocephalus, cerebral/spinal hematoma, inflammatory disease, CNS infection (e.g., encephalitis or meningitis), neoplasm, toxic exposure, metabolic disorder (including hypoxic or hypoglycemic episodes), or endocrine disorder, or any significant medical conditions that, in the opinion of the investigator, would prohibit their participation in the study.
• As assessed by the central reader, MRI evidence of (a) more than three lacunar infarcts, (b) territorial infarct or macroscopic hemorrhage, or (c) deep white matter lesions corresponding to a Fazekas score of 3
• Any contra-indication to undergo MRI, as judged by local PI or radiologist, including but not limited to presence of pacemaker, aneurysm clips, artificial heart valves, ear implants, ventriculoperitoneal shunt, foreign metal objects in the eyes, skin or body or any other circumstance which would contra-indicate an MRI scan or impair MRI image quality, or history of claustrophobia or of not tolerating MRI scanning procedures
• History or active presence of any of the following neurological, psychiatric or medical conditions:
• Large vessel stroke
• Peripheral or CNS demyelinating disease
• Chronic and/or recurrent fungal, bacterial or opportunistic infections
• Myocardial infarction or unstable angina within the previous 12 months
• Clinically relevant or significant ECG abnormalities, including ECG with QT interval corrected for heart rate using Fridericia's formula (QT interval corrected for heart rate using Fridericia's formula) > 450 msec (males) or > 470 msec (females).
• Congestive heart failure, NYHA Class 3 or 4
• Autoimmune disease (e.g., Systemic Lupus Erythematosis (SLE), or symptoms suggestive of a lupus-like syndrome, multiple sclerosis, rheumatoid arthritis, Type 1 diabetes mellitus, inflammatory bowel disease, psoriasis, etc.)
• Immunocompromised systemically due to continuing effects of immune suppressing medication
• Current or previous hepatitis B infection (defined as positive test for hepatitis B surface antigen (HbSAg) and/or hepatitis B core antibody (anti-HBc).
• Participants with immunity to hepatitis B (if due to natural infection defined as negative HBsAg, positive hepatitis B antibody (anti-HBs) and positive anti-HBc; if due to vaccination defined as negative HBsAg, negative anti-HBc and positive anti-HBs are eligible to participate in the study
• For patients with resolved HBV infection, if anti-HBc negative, HBV DNA testing is needed prior to initiating study drug j. History or positive test at Screening for hepatitis C virus antibody (anti-HCV) in the absence of treatment resulting in cure k. History or positive test at Screening for human immunodeficiency virus (HIV) l. History of untreated or incompletely treated tuberculosis or a positive tuberculosis IGRA test.
• m. History of malignancy other than successfully treated, non-metastatic cutaneous squamous or basal cell carcinoma or localized carcinoma in situ of the cervix n. Major depressive episode requiring initiation of medication or hospitalization within the previous 90 days o. Seated blood pressure > 150/90 on 3 separate determinations p. Presence of hallucinations or delusions q. Psychiatric disorder (schizophrenia, schizoaffective disorder, etc.) associated with psychosis r. Active infection(s) requiring treatment with intravenous anti-infectives within 30 days, or oral/intramuscular anti-infectives within 14 days prior to baseline s. Major surgery within 12 weeks of screening t. Blood donation of 1 unit or more within 8 weeks prior to the first dose of study medication
• Any of the following laboratory abnormalities at Screening
• Screening values for hemoglobin < 12 g/d for men or < 11 g/dL for women or other clinically significant hematological abnormality
• Any serum chemistry value (e.g., AST, ALT, alkaline phosphatase, CK, total bilirubin etc. > 2x the upper limit of normal on 2 successive determinations less than 2 weeks apart
• Serum creatinine above the ULN or eGFR < 60 mL/min/1.73 m2
• Platelet count, INR, PT or PTT not within the normal range or other risk for increased or uncontrolled bleeding
• Any other significant medical conditions that, in the opinion of the investigator, would prohibit participation in the study, including inability to tolerate the MRI scan
• For participants agreeing to lumbar puncture: Presence of contra-indication to lumbar puncture as judged by local PI (e.g., known X-ray or other evidence of significant lumbar spine abnormalities or history of lumbar surgery with sequalae that would interfere with or pose risks from the procedure; platelet count below 50,000 cells/mL; need for anticoagulant or antiplatelet medications other than aspirin at a dose of < 100 mg/day or clopidogrel (see item 10 (g) below))

Where it is running

• University of Colorado Anschutz — Aurora, Colorado, United States (enrolling)
• Massachusetts General Hospital — Boston, Massachusetts, United States (enrolling)
• Parkinson's Disease & Movement Disorders Center of Boca Raton — Boca Raton, Florida, United States
• Emory University School of Medicine — Atlanta, Georgia, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• University of Minnesota — Minneapolis, Minnesota, United States
• Washington University — St Louis, Missouri, United States
• Cleveland Clinic Lou Ruvo Center for Brain Health - Las Vegas — Las Vegas, Nevada, United States
• Dartmouth Hitchcock Medical Center — Lebanon, New Hampshire, United States
• Weill Medical College of Cornell University — New York, New York, United States
• Oregon Health & Science University — Portland, Oregon, United States
• University of Pennsylvania — Philadelphia, Pennsylvania, United States
• Medical University of South Carolina — Charleston, South Carolina, United States
• University of Texas Houston Medical Center — Houston, Texas, United States
• University of Texas Health Science Center- San Antonio — San Antonio, Texas, United States
• Cedars Sinai Medical Center — Los Angeles, California, United States
• Montreal Neurological Institute-Hospital at McGill University — Montreal, Quebec, Canada
• Yale Medicine — North Haven, Connecticut, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.